Cysteamine derivatives for oral treatment of seborrhea

ABSTRACT

A method for treating a scalp characterized by an excessive secretion of sebum, to improve the condition thereof by reducing said excessive secretion comprising orally administering to a human being having a scalp so characterized a therapeutic composition comprising an ingestible carrier admixed with, as a non-toxic active compound, cysteine or cysteamine derivatives, the active compound is present in amounts of about 0.75-3 weight percent of the composition which is administered at a rate of about 1-5 mg/kg/day based on the weight of the human being during a period of about 15 days.

This is a division of application Ser. No. 140,956, filed May 6, 1971,now U.S. Pat. No. 3,821,405, which is a continuation-in-part of ourearlier applications Ser. No. 706,652, filed Feb. 19, 1968, now U.S.Pat. No. 3,629,452 and Ser. No. 801,154 filed Feb. 20, 1969, nowabandoned.

The present invention relates to a method for treating a scalpcharacterized by an excessive secretion of sebum, to improve thecondition thereof by reducing said excessive secretion comprising orallyadministering to a human being having a scalp so characterized atherapeutic composition comprising an ingestible carrier admixed with,as a non-toxic active compound, certain cysteine or cysteaminederivatives.

The active compound employed in the present invention is selected fromthe group consisting of a compound having the formula ##EQU1## AND THEACID SALTS THEREOF, WHEREIN N IS 0 OR 1 AND WHEN N IS 0, R₁ and R₂ areselected from the group consisting of hydrogen and CH₃ and when n is 1,R₁ and R₂ are hydrogen;

R₃ is selected from the group consisting of hydrogen and --COR₇ whereinR₇ is selected from the group consisting of hydroxy, alkoxy containing1-5 carbon atoms, glucosamine, --NH--NH₂, --NHOH, ##EQU2## WHEREIN R'REPRESENTS A MEMBER SELECTED FROM THE GROUP CONSISTING OF HYDROGEN ANDALKYL HAVING 1-3 CARBON ATOMS, ##EQU3## WHEREIN R" AND R'" EACHINDEPENDENTLY REPRESENT ALKYL HAVING 1-3 CARBON ATOMS OR TOGETHER WITHTHE NITROGEN ATOM TO WHICH THEY ARE ATTACHED FORM A RING SELECTED FROMTHE GROUP CONSISTING OF MORPHOLINE, PIPERIDINE, PYRROLIDINE ANDN'-methylpiperazine;

A is selected from the group consisting of hydrogen, --CONH₂,nicotinoyl, glutamyl, --COR₄ and --SO₂ R₆ wherein R₄ is selected fromthe group consisting of hydrogen, alkyl having 1-18 carbon atoms,alkenyl having 2-18 carbon atoms, ##EQU4## wherein p is 0-1 and R₅ isselected from the group consisting of hydrogen, alkyl having 1-4 carbonatoms, alkoxy having 1-4 carbon atoms, halogen and acetamide, andwherein R₆ is selected from the group consisting of alkyl having 1-4carbon atoms and ##SPC1##

wherein R₅ has the meaning given above, t is 1 or 2 and when t is 1, Ris selected from the group consisting of linear or branched chain alkylhaving 1-18 carbon atoms, alkenyl having 3-18 carbon atoms, propyne-2yl, mono- or dihydroxyalkyl containing 2-4 carbon atoms,1,2-dichlorovinyl, --C(C₆ H₅)₃, --C(CH₃)₃, --CH(C₆ H₅)₂, --CH(C₆ H₄p-OCH₃)₂, --C(CH₃)₂ (C₆ H₄ p-OCH₃),--CONH₂, ##EQU5## wherein R'" isalkyl having 1-4 carbon atoms and m is 1-2, ##EQU6## wherein m is 1-2and B is selected from the group consisting of ##EQU7## wherein n, R₃and A have the meanings given above, --(CH₂)_(s) --COR₁₀ wherein s is1-5 and R₁₀ is selected from the group consisting of R₇, piperidino,morpholino, pyrrolidino, N'-methylpiperazino and --N(CH₂ --CH₂ OH)₂,--(CH₂)_(z) --R₈ wherein z is 0, 1 or 2 and when z is 0, R₈ is selectedfrom the group consisting of naphthyl-1, napthyl-2, pyridyl-2, pyridyl-2substituted with a member selected from the group consisting of nitroand alkyl having 1-4 carbon atoms, and pyridyl-2-N oxide when R₃ ishydrogen, and when z is 1, R₈ is selected from the group consisting ofnaphthyl-1, naphthyl-2, thienyl-2, tetrahydrofuryl-2, furyl-2,pyridyl-2, pyridyl-2 substituted with a member selected from the groupconsisting of nitro and alkyl having 1-4 carbon atoms, andpyridyl-2-N-oxide and when z is 2, R₈ is selected from the groupconsisting of pyridyl-2, pyridyl-2 substituted with a member selectedfrom the group consisting of nitro and alkyl having 1-4 carbon atoms andpyridyl-2-N-oxide, and ##SPC2##

wherein x is 0-2 and wherein when q is 1, 2 or 3, R₉ is selected fromthe group consisting of hydrogen, halogen, alkoxy having 1-5 carbonatoms and linear or branched chain alkyl having 1-4 carbon atoms, andwhen q is 1, R₉ is selected from the group consisting of acetamido,amino, phenoxy, cyclohexyl, methylenedioxy, trifluoromethyl, nitro,phenyl, dialkylamino wherein each alkyl moiety has 1-5 carbon atoms,alkylthio having 1-5 carbon atoms, alkylsulfinyl having 1-5 carbon atomsand alkyl-sulfonyl having 1-5 carbon atoms, and when t is 2, R isselected from the group consisting of alkylene having 2-4 carbon atoms,alkylene having 2-4 carbon atoms and substituted with 1-2 hydroxygroups, butenylene and --(CH₂)₂ --SO₂ --(CH₂)₂ --.

When the above active compounds contain at least one primary aminegroup, they are preferably used as salt with an inorganic or organicacid selected from the group consisting of hydrochloric, hydrobromic,sulfuric, phosphoric, p-toluene sulfonic, dihydrocinnamic, cinnamic,mandelic, salicylic, tropic, oxalic, malic, tartaric, succinic, acetic,lactic, 3-hydroxy butyric, fumaric, undecylenic, phenylacetic,monochloroacetic, trichloroacetic, glycolic, nicotinic, p-aminobenzoic,glutamic, aspartic, citric, pentothenic, crotonic acid and ascorbic.

However, when the active compounds carry both an amine group and acarboxylic acid function it must be used in order to break the internalsalt an inorganic acid or a strong organic acid such asp-toluenesulfonic acid or trichloracetic acid.

In a related embodiment of the present invention the active compound isselected from the group consisting of a compound having the formula:

1. ##EQU8## wherein R is selected from the group consisting of --C(C₆H₅)₃, --CH(C₆ H₅)₂, --CH₂ --C₆ H₅ and --(CH₂)_(n) --COOR' wherein n is1-4, R' is selected from the group consisting of hydrogen and --CH₃ andR" is selected from the group consisting of hydrogen and --COCH₃ ;

2. the hydrochloride of the compound in (1) above;

3. a compound having the formula ##EQU9## wherein R₁ and R₂ are eachhydrogen; n is 0 or 1; R₃ represents --(CH₂)_(p) -- R₄ wherein p is 0, 1or 2

when p = 0, R₄ is selected from the group consisting of: C₆ H₅,--C(CH₃)₃ -- C(C₆ H₅)₃ and ##SPC3##

when p = 1, R₄ is selected from the group consisting of: C₆ H₅, --COOR₅in which R₅ represents hydrogen, ##EQU10## in which R₅ is hydrogen,##SPC4##

when p = 2, R₄ is selected from the group consisting of: C₆ H₅, --COOR₅in which R₅ represents hydrogen, ##EQU11## wherein R₅ is hydrogen and##SPC5##

R₆ represents a member selected from the group consisting of hydrogenand --COCH₃ ; and

4. the organic and inorganic acid salts of the compound in (3) above,said active compound being present in an amount ranging from 0.75 to 3percent, preferably 0.75 to 1.5 percent, by weight, of said composition.

The organic or inorganic acids useful to prepare the active compound insalt form are hydrochloric, hydrobromic, salicylic, paratoluenesulfonic, citric, phosphoric, malic, tartaric, nicotinic and ascorbicacids.

In another related embodiment of the present invention, the activecompound has the formula

    R -- S -- CH.sub.2 -- CH.sub.2 -- NHZ

wherein R is selected from the group consisting of alkyl, substitutedalkyl, wherein the alkyl moiety has 1-18 carbon atoms, alkenyl whereinthe alkyl moiety has 3-18 carbon atoms, propyne-2 yl and mono anddihydroxy alkyl wherein the alkyl moiety is 2-4 carbon atoms and Z isselected from the group consisting of hydrogen, --COR' and --SO₂ R"wherein R' is selected from the group consisting of lower alkyl having1-6 carbon atoms, phenyl, benzyl and tolyl and R" is selected from thegroup consisting of lower alkyl having 1-4 carbon atoms, phenyl andtolyl, and the non-toxic acid salts thereof. Acids usefully employed toproduce such salts include hydrochloric, phenylacetic, undecylenic andsorbic acids.

The active compounds of this invention may be dissolved in a alimentaryliquid, such as an aqueous or hydro-alcoholic solution which may bearomatized.

They may also be incorporated into any injectable pharmaceuticalexcipient. They may then take, for example, the form of granulas, pillsor tablets. Examples of such compoundings are described in the U.S. Pat.No. 2,888,380.

The composition of this invention is administered at a rate of 1-5mg/kg/day based on the weight of the human being and is generallyadministered during a period of about 15 days. After 15 days, thetreatment may be stopped and then resumed 15 days later.

METHOD OF PREPARATION

In a general manner, active compounds of the present invention can beprepared by the reaction of a thiol, with an organic halide or with anester of methane sulfonic acid of p-toluene sulfonic acid (Method I), orwith a compound having a reactive double bond (Method II), or with anoxirane (Method IV), or with an alcohol (Method III) or with ethyleneimine and its acylation and sulfonylation derivatives (Method IV).

Method I

The most commonly employed procedure is the substitution reaction ofessentially an equimolar ratio of a thiol with an organic halide or amethane sulfonate or a p-toluene sulfonate. The thiol can be aminated ornot. The reaction is carried out under conditions generally orconventionally employed for nucleophilic substitutions including, forinstance, a temperature ranging from 10° to 100°C, atmospheric pressure,and employing a solvent such as water, ammonia, alcohol or dimethylformamide in the presence of a base such as an alkali or alkaline earthhydroxide, or carbonate, an alcoholate, an alkali or alkaline earthamide or even a tertiary aliphatic amine such as triethylamine accordingto the following general reaction:

R -- x + r' -- sh→r -- s -- r' + xh

(x = halogen or --OSO₂ CH₃ or --OSO₂ C₆ H₅)

or

R' -- x + r -- sh→r' -- s -- r + xh

the thiol R--SH or R'--SH can be prepared in situ by basic hydrolysis ofan isothiouronium salt according to the following general reaction:##EQU12##

Method I (alternative)

When R is an aryl radical (X=0), the halide employed is an aryldiazoniumhalide (Vigneaud et al, J.Biol. Chem., 1941, 138, 369 and Clarke andInouye, J.Biol.Chem. 1931, 94.541) and the reaction follows the generalequation:

    ArN.sub.2 CL+R'--SH→Ar--S--R'+N.sub.2 +HCl

Method II

The addition reaction of essentially an equimolar ratio of a thiol witha compound having a reactive double bond is well known and can becarried out, in accordance with known procedures, without a catalyst orin the presence of a peroxide such as ascaridole, benzoyl peroxide, azobis-isobutyronitrile, or in the presence of a base such as thoseemployed in Method I, or even a quaternary ammonium hydroxide or asecondary amine such as piperidine. Representative reaction temperaturesinclude 10° to 100°C and at atmospheric pressure.

The reaction is most generally effected in a medium such as alcohol, forinstance, lower alkanol, water, dioxane, alone or in admixture, with abasic catalyst, so as to obtain a small quantity of thiolate to initiatethe reaction.

The compound utilized having a reactive double bond does not have anamine function. It can, however, contain an amide or sulfonamidefunction.

The radical R can originate from either a compound having a reactivedouble bond (scheme 1) or from a thiol (scheme 2) when R₃ and A areother than hydrogen.

Scheme 1 ##EQU13## Scheme 2 ##EQU14##

Method III

The compounds of the present invention, in which the sulfure atom islinked to a disubstituted or trisubstituted carbon atom, or to a benzylor allyl radical, can conveniently be prepared at a temperature rangingfrom about 50° to 150°C and at atmospheric pressure by reaction ofessentially equimolar amounts of a corresponding tertiary or secondary,benzyl or allyl alcohol, with a thiol, in the presence of a strong acidsuch as gaseous hydrochloric acid, p-toluene sulfonic acid, or a Lewisacid such as the etherate of boron trifluoride, in accordance with thefollowing general reaction: ##EQU15## R'" and R"" only representhydrogen when R" represents aryl or vinyl.

Method IV

Another particularly useful method for preparing compounds of thepresent invention consists of reacting essentially equimolar amounts ofa thiol with an ethylene imine or an acylation or N-sulfonylationderivative thereof at a temperature ranging from about -30° to 80°C. atambient or atmospheric pressures according to the following equationswhich provide an easy method of producing the following compounds:##EQU16##

The reaction is made very easily, in a variety of solvents, chosen as afunction of the solubility of the starting materials. Representativesolvents include alcohols of low molecular weight and chloroform.

Method IV (alternate)

The β-hyroxythioethers can be prepared by an analogous procedure, byreplacing the azinidine by an oxiran, and by effecting the reaction in apolar medium with a basic catalyst, as in Method I according to thefollowing scheme: ##EQU17##

In addition to the above methods, the esters and the amides of thepresent invention can be prepared starting with other compounds.

Thus, esters can be obtained starting with the corresponding acide (R₇ =OH), by reacting an appropriate alcohol therewith to give the desiredester, either at an elevated temperature in the presence of a mineral orsulfonic acid, or at a low temperature in the presence of thionylchloride (Method V).

Amides included in the meaning of R₃ can be prepared simply by thereaction of ammonia, hydrazine, hydroxylamine or an appropriate amine onthe ester noted above, at a temperature generally lower than 30°C(Method VI).

The amides included in A can be conveniently prepared by the action of ahalide or anhydride of a carboxylic acid to produce a carboxamide or bythe action of a sulfonyl halide to produce a sulfonamide when the amideis formamide, the amide is prepared by action of formic acid. Thereaction conditions most generally utilized are those ofSchotten-Baumann, i.e., in water, in the presence of an alkalinehydroxide, or their rearrangement in an organic medium (aromatichyrocarbon, generally a chlorinated solvent) in the presence of a basesuch as pyridine or a tertiary amine, for example, trialkylamine (MethodVII).

When it is desired to prepare acylated compounds having an alcoholfunction, they can be obtained by the action of an amine on a lactone,the reaction being catalyzed by an alkaline alcoholate.

In the case of substituted acetamides, acetylation of the amine canoften advantageously be effected by means of acetic anhydride in anacetic acid medium in the presence of concentrated sulfuric acid.

It will be noted, however, that the majority of the amides included inthe meaning of A are in addition easily produced by one or more ofMethods I-IV.

Finally, compounds of the type where A equals --CONH₂ are prepared bythe action, in an aqueous or aqueous alcoholic medium, of an alkalinecyanate on a compound of the type A=H, in the presence of an equivalentamount of mineral acid, preferably, hydrochloric acid (Method VIII), thestarting compound being obtained according to Methods I-IV.

The preparation of the salts of the active compounds is generallycarried out by first dissolving the acid in an appropriate solvent andthen pouring to this solution either a solution of the active compoundin the same solvent or the active compound alone. The solvent must notbe a solvent of the salt.

To prepare hydrochlorides, it is more convenient to dissolve the activecompound in an appropriated solvent and then to bubble in the solution aslight stream of hydrogen chloride.

Representative Examples of Preparing Active Compounds According to theForegoing General Reactions EXAMPLE 1

N-(2-benzylthioethyl)nicotinamide: (Method VII) ##EQU18##

30 grams of ethyl nicotinate and 80 grams of 2-benzylthio ethylamine areheated for 12 hours at 170°-180°C. The ethane liberated during thereaction is removed by means of a Dean Stark apparatus. After cooling,the reaction mixture is dissolved in 400 cc of carbon tetrachloride; byaddition of petroleum ether, the N-(2-benzylthioethyl)nicotinamidecrystallizes: 47 g. By crystallization in a mixture of carbontetrachloride and cyclohexane, there is recovered colorless crystals ofthe above product melting at 79°C.

    ______________________________________                                        Analysis:          N       S                                                  ______________________________________                                                 Calculated, %                                                                           10.3    11.8                                                        Found, %  10.4    11.9                                               ______________________________________                                    

By bubbling HCl gas into an acetone solution of the above product, thehydrochloride thereof is recovered, which melts at 135°C.

EXAMPLE 2

5-p-toluenesulfonamido 3-thia hexanedioic acid: ##SPC6##

17.9 grams of 3-carboxymethylthio alanine are dissolved in 200 cc ofnormal soda. There are added under agitation 24 grams of p-toluenesulfonyl chloride then, in 3 hours, 100 cc of normal soda. Thesuspension is agitated again for 5 hours at ambient temperature, thenfiltered. The filtrate, acidified with HCl, is extracted with ethylacetate. After evaporation of the ethyl acetate, there remains a yellowsolid which crystallizes in water. 20 grams of the above product incrystalline form are obtained having a melting point of 152°C.

    ______________________________________                                        Analysis:          C       H       S                                          ______________________________________                                                 Calculated, %                                                                           43.23   4.53    19.23                                               Found, %  43.19   4.48    19.24                                      ______________________________________                                    

EXAMPLE 3

2-(2-p-toluenesulfonamido ethylthio)pyridine N-oxide (Method VII)##SPC7##

To a solution of 4.12 g of 2-β-aminoethylthio pyridine N-oxidehydrochloride in 60 cc of water, there are added 4 cc of 5N soda, then3.8 g of p-toluenesulfonyl chloride. The mixture is agitated for 5 hoursat ambient temperature. The pH is maintained a 9.5 by the addition ofnormal soda. The precipitate is filtered and crystallized in aqueousethanol. Yield = 88%. Fusion point: 201°C.

    ______________________________________                                        Analysis:          N       S                                                  ______________________________________                                                 Calculated, %                                                                           8.64    19.77                                                       Found, %  8.77    19.85                                              ______________________________________                                    

EXAMPLE 4

3-(2-pyridyl methylthio) alanine (Method I) ##SPC8##

There are added, over a 15 minute period, 96 cc of 10 N soda to anaqueous solution of 54 g of cysteine hydrochloride. The solutionobtained is treated by a cation exchange resin and the product absorbedon the resin is liberated witn an ammoniacal solution. The eluate isevaporated and the residue is crystallized in a mixture of methanol andisopropyl ether. There is thus recovered 49 g of whitish crystalsmelting at 190°C.

    ______________________________________                                        Analysis:          N       S                                                  ______________________________________                                                 Calculated, %                                                                           13.26   15.10                                                       Found, %  13.23   15.32                                              ______________________________________                                    

EXAMPLE 5

3-o-chlorobenzylthio alanine and the corresponding methyl ester (MethodI). ##SPC9##

In 400 cc of ethanol containing 6.9 g of sodium, there are introduced15.75 g of cystein hydrochloride, then a solution of 16 g ofo-chlorobenzyl chloride in 20 cc of ethanol. The mixture is heated for 1hour at 50°C. After cooling, there are added 400 cc of water and 30 ccof acetic acid. The product crystallizes and is filtered and washed withwater. Yield: 20.8 g. Fusion point is 220°C.

    ______________________________________                                        Analysis:          C        H       N                                         ______________________________________                                                 Calculated, %                                                                           48.87    4.92    5.70                                               Found, %  48.61    4.68    5.42                                      ______________________________________                                    

15 grams of the product obtained above are put into suspension in 15 ccof methanol, in which there is bubbled a stream of dry gaseous HCl for30 minutes. The reaction mixture is left standing for 2 hours at ambienttemperature, evaporated to dryness, the oily residue being dissolved in30 cc of methanol. The product is crystallized by the addition ofdiethyl oxide. Yield = 90%. Fusion point 150°C.

    ______________________________________                                        Analysis:          C        H       N                                         ______________________________________                                                 Calculated, %                                                                           44.60    5.10    4.72                                               Found, %  44.52    5.32    4.65                                      ______________________________________                                    

EXAMPLE 6

2,2'-thio diethylurea (Method I and VII) Method I: ##EQU19##

There are heated under reflux for 30 minutes, 66.3 g of thiourea and145.6 g of β-bromoethylurea in 600 cc of isopropanol. The precipitate(185 g) is filtered, washed with isopropanol and dissolved in 900 cc ofwater. There is added to this solution during a 15 minute period, asolution of 30.45 g of soda in 150 cc of water and the resulting mixtureis heated in a boiling water-bath for 1 hour under nitrogen. The waterbath is removed and there is again introduced 150 cc of a soda solution(30.45 g soda), then a solution of 127.15 g of β-bromoethylurea in 150cc of water.

The reaction mixture is left standing overnight at ambient temperature.The crystallized product is then filtered, yielding 126 g of whiteproduct melting at 234°C. Method VIII: ##EQU20##

To a solution of 92.4 g of 2,2'thio diethylamine in 70 cc of water,there is added with agitation 133 cc of 11.6 N hydrochloric acid whilecooling so as to maintain the temperature below about 25°C. Then thereis added sufficiently rapidly, a solution of 127 g of potassium cyanate(98%) in 150 cc of water. The reaction mixture is left standingovernight and the resulting precipitate is filtered, dried andcrystallized in water, yielding 128 g of white crystals, the fusionpoint of which is 234°C.

    ______________________________________                                        Analysis:          N        S                                                 ______________________________________                                                 Calculated, %                                                                           27.18    15.53                                                      Found, %  27.15    15.32                                             ______________________________________                                    

EXAMPLE 7

3,3'(1,4 dithio butene-2-diyl)dialanine (Method I) ##EQU21##

There is added dropwise a solution of 21.4 g of 1,4 dibromo butene-2 in200 cc of ethanol to a solution of 35.10 g of the hydrochloride ofcysteine monohydrate and 40 cc of 10 N soda in 200 cc of water and 300cc of ethanol. The mixture is agitated for 6 hours at ambienttemperature. The precipitate which forms is filtered and crystallized ina mixture of methanol and water. There is obtained a yield of 97% of awhite solid.

    ______________________________________                                        Analysis:          C        H        N                                        ______________________________________                                                 Calculated, %                                                                           40.79    6.16     9.51                                              Found, %  40.74    6.23     9.23                                     ______________________________________                                    

EXAMPLE 8

3-β-ureidoethylthio alanine (Method I) ##EQU22##

26.25 g of cysteine hydrochloride and 27.83 g of βbromoethylurea aredissolved in 150 cc of water under nitrogen. A solution of 13.35 g ofsoda in 30 cc of water is added during a 40 minute period and themixture is heated for 3 hours at 50°C. After cooling, there is added tothe solution, 4 times its volume of water and the resulting mixture ispassed over a cation exchange resin. After washing with water, theproduct fixed on the resin is eluted with an ammoniacal solution. Theeluate is evaporated to dryness and the residue is crystallized in anaqueous methanol solution. There are obtained 19.5 grams of the whiteproduct melting at 220°C with decomposition.

    ______________________________________                                        Analsysis:         C        H        S                                        ______________________________________                                                 Calculated, %                                                                           34.80    6.28     15.46                                             Found, %  34.84    6.20     15.62                                    ______________________________________                                    

EXAMPLE 9

3-(4-methoxycarbonylbutylthio)alanine hydrochloride (Method I) ##EQU23##

To a solution of 8.77 g of cysteine hydrochloride monohydrate in 150 ccof methanol, there are added, successively, 7.6 g of potassium, then,during a 30 minutes period, 10.45 g of methyl ω-bromopentanoate.

The mixture is heated for 6 hours under reflux, then filtered aftercooling. The precipitate is dissolved in a minimum amount of water andthe solution obtained is acidified with concentrated hydrochloric acid.The desired product precipitates (10.2 g.). It can be crystallized inmethanol by adding diethyl oxide. White crystals are produced which meltat 160°C.

    ______________________________________                                        Analysis:          N       S                                                  ______________________________________                                                 Calculated, %                                                                           5.16    11.85                                                       Found, %  5.46    12.03                                              ______________________________________                                    

EXAMPLE 10

2-(5-methoxycarbonyl pentylthio)ethylamine hydrochloride (Method I)

    ch.sub.3 oco(ch.sub.2).sub.5 --s--ch.sub.2 ch.sub.2 nh.sub.2.hcl

There are added successively, to a solution of 2.6 g of potassium in 100cc of methanol, 4.5 g of β-mercaptoethylamine hydrochloride, then slowly8.2 g of methyl ω-bromohexanoate.

The mixture is heated for 3 hours under reflux. After cooling, it isacidified with gaseous hydrochloric acid and filtered. The filtrate isevaporated to dryness and the oily residue (8 g) crystallizes rapidly.The product melts at 80°C after crystallization in a mixture of methanoland diisopropyl oxide.

    ______________________________________                                        Analysis:        Cl                                                           ______________________________________                                        Calculated, %    14.70                                                        Found, %         14.78                                                        ______________________________________                                    

EXAMPLE 11

3-(2-p-toluenesulfonamidoethylthio) alanine (Method I) ##EQU24##

To a suspension of 17.55 g of cysteine hydrochloride monohydrate and 37g of 2-p-toluenesulfonamido ethyl p-toluene sulfonate in 500 cc ofmethanol, there is added, during a 1 hour period, at 50°C. a solution of19.6 g of potassium at 85% in 500 cc of methanol.

The potassium chloride and potassium p-toluene sulfonate are removed byfiltration. The mother liquor is evaporated to dryness, leaving an oilwhich is mixed with water and acidified with acetic acid. The productprecipitates and is crystallized in water. Yield is 29 g. Fusion pointis 215°C.

EXAMPLE 12

2-methylthioethylammonium phenylacetate (Method I)

    ch.sub.3 s--ch.sub.2 --ch.sub.2 --n.sup.+h.sub.3 o.sup.-.sub.2 c--ch.sub.2 --c.sub.6 h.sub.5

there are added, progressively and with intense agitation, 41 g of2-bromo ethylamine hydrobromide to a solution of sodium methanethiolatein ethanol (starting with 9.6 g of methane thiol and 9.2 g sodium).

The mixture is agitated for 1 hour at ambient temperature, then heatedunder reflux for 30 minutes. After cooling, the mixture is diluted with200 cc of ether and then filtered to remove therefrom the mineral salts.The filtrate is concentrated and the resulting oily residue isfractionated. The fraction distilling at 42°C under 16 mm Hg, isrecovered and yields 13.6 g (75%) of 2-methylthioethylanine which areadded, in a solution of ether (300 cc), to a solution of phenyl-aceticacid (0.15 mol) in the same solvent. The salt formed crystallizes, inproportion to the addition, in the form of white needles (33.5 g) whichare purified by crystallization in ethyl acetate. Yield = 92%. Fusionpoint: 92°-94°C.

    ______________________________________                                        Analysis:   N              S                                                  ______________________________________                                        Calculated, %                                                                             6.16           14.10                                              Found, %    6.11           14.01                                              ______________________________________                                    

EXAMPLE 13

3-(9,11 dihydroxy 10,10-dimethyl 4,8-dioxo 3,7-diazaundecylthio)alanine- (Method IV) ##EQU25##

10 g of calcium pantothenate are dissolved in 10 cc of water. To thissolution are added, in succession, 2.66 g of oxalic acid in a minimum ofwater and 10 cc of triethylamine. The calcium oxalate formed is removedby filtration. There is obtained triethylamine pantothenate in the formof an oil by concentrating the filtrate to dryness.

This salt is dissolved in 25 cc of anhydrous dimethyl formamide and thesolution is cooled to -5°C. Then dropwise, while maintaining thetemperature at -5°C, there is added a solution of 4.1 g of ethylchloroformate.

The mixture is added dropwise to a solution of 25 g ethyleneimine and 5g of triethylamine in 50 cc of ethyl acetate while maintaining thetemperature at -5°C. The mixture is agitated for 20 minutes at -5°C.

During a period of about 15 minutes, there is added a filtered solutionof 6.6 g of cysteine hydrochloride and 4.2 g of triethylamine in 20 ccof dimethyl formamide. After 30 minutes at 0°C, the solution is filteredand the filtrate is evaporated to dryness under a vacuum. The oilyresidue is dissolved in ethyl ether and after standing, crystallizes inthe form of a white hygroscopic product, the fusion point of which is75°-80°C. Yield = 75%.

The proportion of carboxylic acid and amine functions correspond totheory.

EXAMPLE 14

2-amino-4-thia nonadioic acid (Method II) ##EQU26##

10 g of allylacetic acid are added dropwise to 15.75 g of cysteinehydrochloride. Under intense agitation, there are added 10 mg of benzoylperoxide. The mixture becomes heated and liquifies and is maintained for1 hour at 80°C. After cooling, it is dissolved in 50 cc of 2 N soda. Theprecipitate that forms is filtered and washed with water. Yield: 16.5 g.After crystallization is dilute hydrochloric acid, the product melts at230°C with decomposition.

The proportion of carboxylic acid function corresponds to theory.

EXAMPLE 15

Bis[2-(2,2-dimethoxyethylthio)ethylamine]oxalate (Method I) ##EQU27##

To a solution of 4.6 g of sodium in 150 cc of ethanol, there are added11.35 g of β-mercaptoethylamine hydrochloride, the, dropwise 16.9 g ofthe bromide of 2,2'-dimethoxyethyl bromoacetaldehyde dimethylacetal.

The mixture is heated for 2 hours under reflux. The mineral salts arefiltered after cooling and the mother liquor is concentrated. The oilyresidue is distilled in 17 mm Hg at 125°-130°C. Yield = 74%.

The 12.2 g of 2-(2,2-dimethoxyethylthio)ethylamine obtained above aredissolved in 50 cc of ethanol and added to a solution of 4.65 g of thedihydrate of oxalic acid. The salt formed cyrstallizes by addition ofethyl ether, after cooling. By crystallization in 2-propanol and ethylether, white crystals are obtained. Fusion point: 170°-172°C. Weight:28.6 g

    Analysis:   N              S                                                  ______________________________________                                        Theory, %   6.66           15.25                                              Found, %    6.58           15.18                                              ______________________________________                                    

EXAMPLE 16

2-(2-p-methoxyphenyl 2-propylthio)ethylamine hydrochloride (Method III)##EQU28##

To a solution of 11.25 g of β-aminoethylthio in 50 cc acetic acid thereare added successively 15.42 g of p-methoxy phenyl dimethyl carbinol anda solution of boron trifluoride in acetic acid. The mixture is heated 30minutes at 60°C, then cooled. This solution is added dropwise to a 10%solution of sodium acetate, which is extracted three times with ethylether and dried over sodium sulfate. By bubbling gaseous hydrochloricacid in the etherified solution, the product is produced as a whiteprecipitate. Fusion point with decomposition: 172°-174°C. Yield: 62%.

    ______________________________________                                        Analysis:  C           H          N                                           ______________________________________                                        Theory, %  55.05       7.70       5.35                                        Found, %   54.98       7.85       5.21                                        ______________________________________                                    

EXAMPLE 17

2-acetamido 3-(2,4-dichlorobenzylthio(propionic acid (Method I and VII)##SPC10##

To a solution of 6.9 g of sodium in 400 cc of absolute ethanol, thereare added, successively, 15.75 g of cysteine hydrochloride and 19.54 gof 2,4-dichloro benzyl chloride.

Then the mixture is heated at 50°C for a period of one hour. By adding600 cc of water and 30 cc of acetic acid, the product crystallizes inthe form of needles. Fusion point 205°-210°C.

24.5 g of this product, 2-amino 3-(2,4-dichlorobenzylthio)propionicacid, are acetylated in accordance with the conventionalSchatten-Baumann reaction. There is obtained a precipitate which iscrystallized in 40% ethanol, weight: 23.85 g. Fusion point: 134°-135°C.

    ______________________________________                                        Analysis:  C           H          N                                           ______________________________________                                        Theory, %  44.73       4.06       4.34                                        Found, %   44.78       4.17       4.35                                        ______________________________________                                    

EXAMPLE 18

3-[Bis-(p-methoxy phenyl) 3-methylthio]alanine (Method III) ##EQU29##

A solution of 17.56 g of cysteine hydrochloride monohydrate in 85 cc ofacetic acid is heated with agitation at 60°C. Then there is added,sucessively, 24.4 g of bis-(p-methoxyphenyl)carbinol and 20.7 g of borontrifluoride in acetic acid. The mixture is heated at 80°C for a periodof 15 minutes, then cooled to 10°C. Then, by adding a solution of 48 gof sodium acetate in 50 cc of water and 150 cc of ethanol, the productprecipitates. After crystallization in a mixture of water anddimethylformamide, there are obtained white crystals, the fusion pointof which is 209°-211°C. Yield: 85%.

    ______________________________________                                        Analysis:  C           H          N                                           ______________________________________                                        Theory, %  62.22       6.09       4.03                                        Found, %   62.38       6.15       4.22                                        ______________________________________                                    

EXAMPLE 19

2-allylthioethylammonium malate (Method I)

    ch.sub.2 =ch--ch.sub.2 --s--ch.sub.2 --ch.sub.2 --n.sup.+h.sub.3 o.sup.+.sub.2 c--ch (oh)ch.sub.2 --cooh

24.2 g of allyl bromide are added dropwise to a solution of 22.7 g ofβ-aminoethylthio in 150 cc of ethanol containing 9.2 g of metallicsodium. The mixture is heated under reflux for 1 hour. The resulting oilphase is decanted and is dissolved by adding ether thereto in order toeliminate by filtration the mineral salts. The filtrate is concentratedunder vacuum, leaving an oily residue. Weight: 38.1 g. The oily residueis dissolved in 100 cc of absolute ethanol and 43.5 g of malic acid areadded with agitation in small portions. By adding ether, the productforms as a white precipitate which, after crystallization in 2-propaol,melts at 94°C. Yield: 65%.

    ______________________________________                                        Analysis:                                                                              N         S         C       H                                        ______________________________________                                        Theory, %                                                                              5.57      12.76     43.01   6.81                                     Found, % 5.56      12.66     43.04   6.90                                     ______________________________________                                    

EXAMPLE 20

2-amino 4-β-aminoethylthio butyric acid (Method I) ##EQU30##

There are added, in small amounts, 21.52 g of sodium to a suspension of40 g of methionine in 1.5 l of liquid ammonia. After the addition, themixture is maintained under agitation for 4 hours. There is then addedto the mixture sufficient ammonium chloride to decolorize the solution.The ammonia is evaporated overnight at ambient temperature and the whiteresidue is dissolved in 200 cc of water. There is added, over a 2-hourperiod, a solution of 55 g of 2-bromo ethylamine hydrobromide in 300 ccof water. The mixture is agitated for 3 hours at 20°C and then for 3hours at 50°C. The reaction product is then treated with DOWEX Resin 50W, and then eluted by means of an ammoniacal solution. The eluate isconcentrated under vacuum. The solid residue is admixed with 75 cc ofwater, neutralized with 52 cc of 6N hydrochloric acid and treated withanimal charcoal. There is obtained after filtration a colorless solutionwhich is then concentrated under vacuum. The solid residue iscrystallized in a mixture of water, methanol, acetone and is in the formof white crystals (38 g) melting at 216°-217°C.

    ______________________________________                                        Analysis - C.sub.6 H.sub.15 ClN.sub.2 O.sub.2 S                                               C       H       N     HCl                                     ______________________________________                                        Calculated, %   33.66   7.03    13.05 17.03                                   Found, %        33.61   7.18    13.08 17.08                                   ______________________________________                                    

EXAMPLE 21

S-β-aminoethyl mercaptobutyric acid (Method I) ##EQU31##

A solution of 51 g of 2-thiolannone in 50 cc of methanol is added to asolution of 150 cc of 10 N soda, 400 cc of water and 500 cc of methanol.In the resulting solution, there is introduced, in several portions, 103g of β-bromoethylamine hydrobromide. The mixture is heated under refluxfor 3 hours. The solution is treated with an ion exchange resin inhydrogen form, in accordance with conventional procedures. Theconcentrated eluate provides a solid residue which is washed in ethanoland filtered. Yield: 62.5 g. Fusion point: 171°C.

The proportion of acid and amine functions conform to theory.

EXAMPLE 22

S-β-ureidoethylmercaptoacetic acid (Methods I and VIII) ##EQU32##

To a solution of 34.1 g of β-mercaptoethylamine hydrochloride in 200 ccof water there is added a solution of 24.3 g of potassium cyanate in 80cc of water, then 36 g of sodium monochloroacetate in 200 cc of water.The solution is heated at 50°C for 2 hours while maintaining the pH at 6by the addition of 2N soda. The mixture is then acidified, concentratedto dryness and washed with a mixture of water and ethanol. Afterfiltration, there is produced 42 g of the product which melts at 135°C.

    ______________________________________                                        Analysis: C        H         N       S                                        ______________________________________                                        Calculated, %                                                                           33.69    5.65      15.72   17.99                                    Found, %  33.79    5.67      15.62   18.07                                    ______________________________________                                    

EXAMPLE 23

2-methoxycarbonylmethylthioethylamine hydrochloride (Method V)

    ch.sub.3 o--co--ch.sub.2 --s--ch.sub.2 --ch.sub.2 --nh.sub.2.hcl

13.5 g of S-(β-aminoethyl)mercaptoacetic acid and 10.8 g of2,2-dimethoxy propane are added, successively, to a solution of 7.3 g ofgaseous hydrochloric acid in 20 cc of methanol. The solution ispermitted to stand for 12 hours at ambient temperature. The flasksformed (17.5 g) are filtered and washed with ethyl acetate. Fusion point= 100°C.

    ______________________________________                                        Analysis:        Cl                                                           ______________________________________                                        Calculated, %    19.1                                                         Found, %         19.2                                                         ______________________________________                                    

EXAMPLE 24

N-(2-benzylthioethyl)2,4-dihydroxy 3,3-dimethyl butyramide (Method VII)##EQU33##

13 g of pantolacetone with a few drops of a methanol solution of sodiummethylate are added to a solution of 16.7 g 2-benzylthio ethylamine in50 cc of ethanol. The mixture is heated for 6 hours at 60°-65°C.

After cooling, the product is crystallized by addition of diethyl oxide.White crystals (23.8 g) melt at 70°C.

EXAMPLE 25

2-β-hydroxyethylthioethylamine hydrochloride (Method IV) ##EQU34##

There are added in 1 hour, 39 g of 2-mercapto ethanol in 50 cc ofethanol to a solution of 21.5 g of ethyleneimine in 100 cc of ethanol.The mixture is maintained for 10 hours at 40°C and then concentrated todryness. The oily residue (56 g) is fractionated under vacuum (1.5 mmHg) and the fraction distilling at 113°-116°C (48 g) is recovered.

By the action of gaseous hydrochloric acid on an ethanol solution of thedistilled amine, there is obtained the hydrochloride in the form ofcrystals (59 g) which melt at 45°-48°C.

    ______________________________________                                        Analysis:        HCl                                                          ______________________________________                                        Calculated, %    23.15                                                        Found, %         23.10                                                        ______________________________________                                    

EXAMPLE 26

3,3'-(2',2-sulfonyl diethylthio)dialanine and the N,N'-diacetylderivative thereof. (Method II and VII) ##EQU35##

To a solution of 70.2 g of cysteine hydrochloride monohydrate in 300 ccof water, there is added, successively, 53 cc of 8 N soda, 0.5 cc ofconcentrated ammonia and after 30 minutes, a solution of 23.6 g ofdivinyl sulfone in 300 cc of water. After two hours under agitation, thereaction mixture is filtered and the precipitate (67 g) is washed withwater and with ethanol.

    ______________________________________                                        Analysis:   C          H          N                                           ______________________________________                                        Calculated, %                                                                             33.31      5.59       7.77                                        Found, %    32.99      5.56       7.72                                        ______________________________________                                    

21.6 g of the precipitate obtained above are dissolved in 30 cc of waterand 15 cc of 8N soda. To this solution, there is added, successively, 60cc of acetic anhydride and 112.8 cc of 8N soda.

Agitation of the mixture is continued for some time and it is acidifiedwith 147.6 cc of ION hydrochloric acid. The precipitate formed infiltered and washed with water. Yield: 21.42 g. Fusion point: 196°C.

    ______________________________________                                        Analysis:   C          H          N                                           ______________________________________                                        Calculated, %                                                                             37.82      5.44       6.30                                        Found, %    37.38      5.43       6.35                                        ______________________________________                                    

EXAMPLES OF COMPOSITIONS AND THEIR USE IN ACCORDANCE WITH THIS INVENTIONEXAMPLES 27-34

The following composition is prepared and is usefully employed to reduceexcessive secretion of sebum on the scalp. It is orally administered inthe form of drops.

    ______________________________________                                        3-allyl thio alanine hydrochloride                                                                    1       g                                             Glycerine               40      g                                             Ethyl alcohol           30      g                                             Water, q.s.p.           100     g                                             Lemon tincture (q.s.p. impart a                                               pleasing aroma)                                                               ______________________________________                                    

The oral administration of this composition at the rate of 10 drops eachday for 15 days by a person having greasy hair due to excessivesecretion of sebum substantially improves the condition of the scalp andthe appearance of the hair.

Essentially similar effective results are obtained when the 3-allyl thioalanine hydrochloride is replaced with the following compounds:3-(β-hydroxyethyl thio) alanine, 2-amino, 4-thia dodecanoic acid,2-(2-naphthyl thio) ethyl ammonium disuccinate, 2-(pyridyl-2-methylthio) ethylamine dihydrochloride, 2-cetylthio ethylamine hydrochloride,2-(3,4-dimethoxy benzylthio) ethylammonium malate and 2-amino4-tetradecylthio butyric acid.

EXAMPLES 35-41

The following composition is prepared:

    3-methylthio alanine hydrochloride                                                                    50      mg                                            Glucose                 300     mg                                            Water, q.s.p.           5       ml                                            Orange juice (q.s.p. to impart a                                              pleasant aroma)                                                           

The oral administration of this composition, at the rate of 2 ampouleseach day for 15 days by a person having greasy hair due to excessivesecretion of sebum substantially improves the condition of the scalp andthe appearance of the hair.

Essentially similar effective results are achieved by replacing the3-methylthio alanine hydrochloride with the following compounds:3-(2,4-dichlorobenzylthio)alanine, 3,3'-(2-butene 1,4diyldithio)dialanine, 2-(2,2-dimethoxy ethylthio)ethylaminehydrochloride, S-(3-aminopropyl)mercapto acetic acid,2-(2,4-dichlorocetylthio)ethylamine and 5-dodecanamido 3-thiahexanedioic acid.

EXAMPLE 42-48

Lozenges for oral consumption having the following composition areprepared:

    3-(β-ureidoethylthio)alanine                                                                     20      mg                                            Lactose                 300     mg                                            Powdered gum arabic     100     mg                                            Simple syrup, q.s.p.    500     mg                                        

These lozenges, taken at a rate of 15 each day, by a person havinggreasy hair and scalp due to excessive secretion of sebum substantiallyimproves the condition of the scalp and the appearance of the hair byreducing excessive secretion of sebum.

Essentially similar effective results are achieved by replacing the3-(β-ureidoethylthio)alanine by the following compounds: 3-octylthioalanine, 2-(3,4 methylenedioxybenzylthio)ethylamine hydrochloride,3-(2-pyridyl N-oxide methylthio)alanine, o-fluorobenzylthioethylaminehydrochloride, 2-amino 4-(o-chlorobenzylthio)methyl butyratehydrochloride, and 6-amino 3-thia dimethyl heptanedioate hydrochloride.

EXAMPLES 49-53

Chewable pellets having the following composition are prepared:

    3-(2-pyridyl methylthio)alanine                                                                       2.5     g                                             Sucrose                 200     g                                             Lemon syrup             50      g                                         

These pellets, administered at the rate of a coffee spoonful twice a dayto a person having greasy hair and scalp due to excessive secretion ofsebum substantially reduces excessive secretion of sebum and therebysignificantly improves the condition of the scalp and the appearance ofthe hair.

Essentially similar effective results are achieved by replacing3-(2-pyridyl methylthio)alanine by the following compounds: 6-amino3-thia heptanedioic acid, 2-(undecenyl thio)ethylamine, 3-methylthio2-propionamide dimethyl amino ethyl propionate and 3-benzylthio2-butyramido propionic acid.

EXAMPLES 54-56

Tablets having the following compositions are prepared:

    5-p-toluenesulfonamido 3-thia                                                 hexane dioicacid        10      mg                                            Lactose                 150     mg                                            Gum arabic              100     mg                                            Starch, q.s.p.          500     mg                                        

These tablets taken at a rate of 10 each day for 20 days by a personhaving greasy hair and scalp because of excessive secretion of sebumeffectively reduces excessive sebum secretion and significantly improvesthe appearance of the hair and scalp condition.

Essentially similar effective results are achieved when5-p-toluenesulfonamido 3-thia hexane dioic acid is replaced by thefollowing compounds: 2,4-dichloro 2-benzyl thio ethylamine aspartate andN-[2-(3,5 dichloro benzylthio) ethyl] trifluoro acetamide.

Table I below lists active compounds which are cysteine derivatives andwhich are usefully employed in the present invention. Table I identifiesthe general method by which the active compounds are prepared inaccordance with methods I-VIII, above, as well as representativecompositions in which they are included for oral administration tohumans having a scalp characterized by excessive secretion of sebum, toreduce said excessive secretion so as to improve the condition of thescalp and to improve the appearance of the hair.

                                      TABLE I                                     __________________________________________________________________________                                  Method of   Form of Amount in                   NO.   Active Compound         Preparation Composition                                                                           Composition                 __________________________________________________________________________    1     3-methylthio alanine    I           Drops as in                                                                           .75 g                                                                 Ex. 27-34                           2     3-methylthio alanine hydrochloride                                                                    I           "       .75                         3     3-isopropylthio alanine I or III    "       .75                         4     3-n-octylthio alanine   I           "       .75                         5     3-(2-ethyl hexylthio)alanine                                                                          I           "       .75                         6     3-dodecylthio alanine   I           "       1.00                        7     3-hexadecylthio alanine I           "       1.00                        8     3-octadecylthio alanine I           "       1.00                        9     3-(9-octadecene-ylthio) alanine                                                                       I           "       1.00                        10    3-allylthio alanine     I           "       1.00                        11    3-allylthio alanine hydrochloride                                                                     I           "       1.25                        12    3-(2-butene-ylthio)alanine                                                                            I           "       1.25                        13    1,2-dichloro 3-vinylthio alanine                                                                      I           "       1.25                        14    3-(2-propyne-ylthio)alanine                                                                           I           "       1.25                        15    3-t-butylthio alanine   III         "       1.25                        16    3,3'-(2-butene 1,4-diyl-dithio)dialanine                                                              I           "       1.50                        17    3-β-hydroxyethylthio alanine                                                                     I or IV(alternative)                                                                      "       1.50                        18    3-(2,3-dihydroxy propylthio)alanine                                                                   IV(alternative)                                                                           Drops as in                                                                           1.50 g                                                                Ex. 27-34                           19    3-(2-hydroxy propylthio) alanine                                                                      IV(alternative)                                                                           "       1.50                        20    3-(2,2-(dimethoxy ethylthio)alanine                                                                   I           "       1.50                        21    3-(3,3-diethoxy propylthio)alanine                                                                    I or II     "       2.00                        22    3-(1,2-propylenedioxy ethylthio)alanine                                                               I           "       2.00                        23    3-(2,2-ethylenedioxy propylthio)alanine                                                               I or II     "       2.00                        24    3-β-ureidoethylthio alanine                                                                      I           "       2.00                        25    3-β-acetamidoethylthio alanine                                                                   I or IV     "       2.00                        26    2-β-p-toluenesulfonamido 3-ethylthio                                     alanine                 I or IV     "       2.50                        27    3-β-phenylacetamidoethylthio alanine                                                             I           "       2.50                        28    3-β-aminoethylthio alanine                                                                       I or IV     "       2.50                        29    3-β-nicotinamidoethylthio alanine                                                                I or IV     "       3.00                        30    3-[2-(2,4-dihydroxy 3,3-dimethyl butyramido)                                  ethylthio] alanine      VII         "       3.00                        31    3-[9,11-dihydroxy 10,10-dimethyl 4,8-dioxo                                    3.7-diaza undecylthio] alanine                                                                        IV          "       3.00                        32    3,3'-thio dialanine     II          "       3.00                        33    3-(ω-amino ω-carboxypropylthio) alanine                                                   I or II     "       3.00                        34    S-(3-alanyl) N-acetyl cysteine                                                                        II          Ampoules as                                                                           50 mg                                                                 in Ex. 35-41                        35    3-(2-naphthyl thio) alanine                                                                           I or II     "       50 mg                       36    S,S'-[2,3-dihydroxy 1,4-butanediyl] bis                                       cysteine                I           "       50 mg                       37    3-(2-thenylthio) alanine                                                                              I           "       50 mg                       38    3-o-chlorobenzylthio alanine                                                                          I           "       50 mg                       39    3-p-chlorobenzylthio alanine                                                                          I           "       50 mg                       40    3-furfurylthio alanine  I           "       50 mg                       41    3-tetrahydrofurfurylthio alanine                                                                      I           "       50 mg                       42    3-(2-pyridyl methylthio) alanine                                                                      I           "       50 mg                       43    3-β-phenylethylthio alanine                                                                      I or II     "       50 mg                       44    3-(2-pyridyl thio) alanine                                                                            I           "       50 mg                       45    3-diphenylmethylthio alanine                                                                          III (and I) "       50 mg                       46    3-(2-pyridyl ethylthio) alanine                                                                       II or I     "       50 mg                       47    3-(2,4-dichloro benzylthio) alanine                                                                   I           "       50 mg                       48    3-(3,4-dichloro benzylthio) alanine                                                                   I           "       50 mg                       49    3-(3,5-dichloro benzylthio) alanine                                                                   I           "       50 mg                       50    3-(2,6-dichloro benzylthio) alanine                                                                   I           "       50 mg                       51    3-o-methoxybenzylthio alanine                                                                         I           Ampoules as                                                                           50 mg                                                                 in Ex. 35-41                        52    3-p-butoxybenzylthio alanine                                                                          I           "       50 mg                       53    3-p-methoxybenzylthio alanine                                                                         I           "       50 mg                       54    3-p-bromobenzylthio alanine                                                                           I           "       50 mg                       55    3-m-fluorobenzylthio alanine                                                                          I           "       50 mg                       56    3-(3,4-dimethoxy benzylthio)alanine                                                                   I           "       50 mg                       57    3-(3,4-methylenedioxy benzylthio)alanine                                                              I           "       50 mg                       58    3-p-fluorobenzylthio alanine                                                                          I           "       50 mg                       59    3-(3,4,5-trimethoxy benzylthio)alanine                                                                I           "       50 mg                       60    3-(2-pyridyl N-oxide methylthio)alanine                                                               I           "       50 mg                       61    3-o-methylbenzylthio alanine                                                                          I           "       50 mg                       62    3-p-methylbenzylthio alanine                                                                          I           "       50 mg                       63    3-(4-t-butyl benzylthio)alanine                                                                       I           "       50 mg                       64    3-o-fluorobenzylthio alanine                                                                          I           "       50 mg                       65    3-(4-isopropyl benzylthio) alanine                                                                    I           "       50 mg                       66    3-(2,4-dimethyl benzylthio) alanine                                                                   I           Lozenges as                                                                           10 mg                                                                 in Ex. 42-48                        67    3-p-trifluoromethyl benzylthio alanine                                                                I           "       10 mg                       68    3-o-trifluoromethyl benzylthio alanine                                                                I           Lozenges as                                                                           10.00 mg                                                              in Ex. 42-48                        69    3-p-acetamidobenzylthio alanine                                                                       I           "       10.00                       70    3-p-dimethylamino-benzylthio alanine                                                                  I           "       10.00                       71    3-p-phenoxybenzylthio alanine                                                                         I           "       15.00                       72    3-p-phenylbenzylthio alanine                                                                          I           "       15.00                       73    3-(4-methylthio benzylthio)alanine                                                                    I           "       15.00                       74    3-(4-propylsulfonyl benzylthio)alanine                                                                I           "       15.00                       75    3-(4-butylsulfonyl benzylthio)alanine                                                                 I           "       15.00                       76    3-(2-methylthio benzylthio)alanine                                                                    I           "       15.00                       77    3-benzylthio alanine    I           "       17.50                       78    2-amino 3-benzylthio propionamide hydro-                                      chloride                VI          "       17.50                       79    3-benzylthio 2-nicotinamido propionate of                                     2-hydroxy 2-propyl      V or VII    "       17.50                       80    3-benzylthio 2-nicotinamido propionic acid                                                            VII         "       17.50                       81    3-ethoxycarbonyl methylthio alaninate                                         of ethyl                V           "       17.50                       82    5-p-toluene sulfonamido 3-thia hexanedioic                                    acid                    VII         "       8.00                        83    5-p-acetamidobenzene sulfonamido 3-thia                                       hexanedioic acid        VII         "       8.00                        84    2-propionamido 3-thia hexanedioic acid                                                                VII         Lozenges as                                                                           8.00                                                                  in Ex. 42-48                        85    2-p-acetamidobenzamido 3-benzylthio                                                                   VII         "       8.00                              propionic acid                                                          86    2-methanesulfonamido 3-dodecylthio                                                                    VII         "       8.00                        87    5-benzamido 3-thia hexanedioic acid                                                                   VII         "       8.00                        88    2-glutamino 3-methylthio propionic acid                                                               VII         "       8.00                        89    5-ureido 3-thia hexanedioic acid                                                                      VIII        "       8.00                        90    N-(2-amino 3-benzylthio propionyl)                                            glucosamine hydrochloride                                                                             VI          "       8.00                        91    2-formamido 4-thia heptanedioic acid                                                                  VII         "       8.00                        92    3-benzylthio 2-(9-octadecene amido)                                           propionic acid          VII         "       8.00                        93    2-amino 3-benzylthio propionhydroxamic                                                                VI          "       15.0                              acid                                                                    94    2-acetamido 3-benzylthio propionhydrazide                                                             VI          "       15.0                        95    2-propionamido 3-benzylthio propion-                                          hydroxamic acid         VI          "       15.0                        96    3-p-ethoxy benzylthio alanine                                                                         I           "       15.0                        97    bis-(p-methoxyphenyl)-3-methylthio alanine                                                            I or III    "       15.0                        98    3-(2-p-methoxyphenyl 2-propyl thio)                                                                   I or III    Chewable                                                                              1.90 g                            alanine                             pellets as                                                                    in Ex. 49-53                        99    3-(2-naphthyl methylthio)alanine                                                                      I           "       1.90 g                      100   3-phenylthio alanine    I(alternative) or II                                                                      "       1.90 g                      101   3-o, m or p-chlorophenylthio alanine                                                                  I(alternative) or II                                                                      "       1.90 g                      102   3-p-fluorophenylthio alanine                                                                          I(alternative) or II                                                                      "       1.90 g                      103   3-o or p-methoxyphenylthio alanine                                                                    I(alternative) or II                                                                      "       1.90 g                      104   3-benzylthio valine     II          "       2.5 g                       105   2-amino 4-benzylthio butyric acid                                                                     I           "       2.5 g                       106   3-carbamyl methylthio alanine                                                                         I           "       2.5 g                       107   3-γ-aminopropylthio alanine                                                                     I           "       2.5 g                       108   3-o-aminophenylthio alanine                                                                           I           "       2.5 g                       109   3-(2-carboxy ethylthio)alanine                                                                        II or I     "       2.5 g                       110   3-β-butoxy carbonyl ethylthio alanine                                                            II          "       3.75 g                      111   3-propoxy carbonylmethylthio alanine                                                                  V           "       3.75 g                      112   3-ω-methoxycarbonyl butylthio alanine                                                           I           "       3.75 g                      113   3-ω-methoxy carbonyl pentylthio alanine                                                         I           "       3.75 g                      114   3-(3-carboxy propylthio)alanine                                                                       I           "       3.75 g                      115   2-amino 4-thia nonanedioic acid                                                                       II          Chewable                                                                              5.0 g                                                                 pellets as                                                                    in Ex. 49-53                        116   2-amino 4-thia decanedioic acid                                                                       I           "       5.0 g                       117   2-amino 4-thia dodecanedioic acid                                                                     I           "       5.0 g                       118   3-carboxymethylthio alanine                                                                           I           "       5.0 g                       119   N-(2-acetamido 3-benzylthio propionyl)                                        glucosamine             VI          "       5.0 g                       120   3-benzylthio 2-(10-undecene-amido) propionic                                  acid                    VII         "       5.0 g                       121   3-benzylthio 2-octadecanamido propionic                                       acid                    VII         "       6.25 g                      122   3-carbamylthio alanine  VIII        "       6.25 g                      123   3-methylthio 2-propionamido propionate of                                     dimethylaminoethyl      V           "       6.25 g                      124   2-acetamido 3-benzylthio propionate of                                        diethylaminoethyl       V           "       6.25 g                      125   3-benzylthio 2-propionamido propionate                                        of 1-butoxy 2-propanol  V           "       7.50 g                      126   5-amino 3-thia hexanedioate of                                                di-(β-piperidinoethyl) hydrochloride                                                             V           "       7.50 g                      127   3,3-(2,2-sulfonyl diethylthio)dialanine                                                               II          "       7.50 g                      128   3-o-nitrophenylthio alanine                                                                           I           "       7.50 g                      129   3-β-piperidinocarbonyl ethylthio alanine                                                         I or II     Tablets as                                                                            6 mg                                                                  in Ex. 54-56                        130   2-acetamido 3-pyrrolidinocarbonylmethyl-                                      thio propionic acid     I           "       6 mg                        131   2-amino 4-ortho-chlorobenzylthio butyrate                                     of methyl hydrochloride I           "       6 mg                        132   2-amino 4-β-amino ethylthio butyric acid                                 hydrochloride           I           "       6 mg                        133   2-propionamido 4-tetradecylthio butyric                                       acid                    VII         "       6 mg                        134   2-amino 4-tetradecylthio butyric acid                                                                 I           "       6 mg                        135   6-amino 3-thia heptanedioic acid                                                                      I           "       6 mg                        136   S,S'-(2 butene 1,4-diyl)bis-homocysteine                                                              I           "       6 mg                        137   N-formyl S-methyl penicillamine                                                                       I or II     "       6 mg                        138   2-amino 4-thia heptanedioic acid                                                                      II or I     "       7,5 mg                      139   S-carboxymethyl cysteinate of methyl                                                                  VII         "       7,5 mg                      140   5-nicotinamido 3-thia hexanedioic acid                                                                VII         "       7,5 mg                      141   5-p-acetamidobenzamido 3-thia hexanedioic                                     acid                    VII         "       7,5 mg                      142   5-p-butoxybenzamido 3-thia hexanedioic acid                                                           VII         "       7,5 mg                      143   5-dodecanamido 3-thia hexanedioic acid                                                                VII         "       7,5 mg                      144   6-amino 3-thia heptanedioate of     Tablets as                                                                            7.50 mg                           dimethyl                V           in Ex. 54-56                        145   5-p-methoxybenzamido 3-thia hexanedioic                                       acid                    VII         "       7.50 mg                     146   2-acetamido 4-thia nonanedioic acid                                                                   VII         "       7.50 mg                     147   3-benzylthio 2-butyramido propionic acid                                                              VII         "       7.50 mg                     148   3-benzylthio 2-propionamido propionic acid                                                            VII         "       7.50 mg                     149   3-benzylthio 2-methanesulfonamido                                             propionic acid          VII         "       7.50 mg                     150   3-benzylthio 2-ethanesulfonamido propionic                                    acid                    VII         "       10.0 mg                     151   3-benzylthio 2-propanesulfonamido                                             propionic acid          VII         "       10.0 mg                     152   3-benzylthio 2-butanesulfonamido propionic                                    acid                    VII         "       10.0 mg                     153   2-acetamido 3-benzylthio propionic acid                                                               VII         "       10.0 mg                     154   2-amino 3-benzhydryl propionate of methyl                                     hydrochloride           V           "       10.0 mg                     155   5-acetamido 3-thia hexanedioic acid                                                                   VII         "       10.0 mg                     156   S-(carboxymethyl) cysteinate of butyl                                                                 I           "       12.5 mg                     157   S-(ethoxy carbonyl methyl) cysteine                                                                   I and V     "       12.5 mg                     158   S-(propoxy carbonyl methyl) cysteine                                                                  I and V     "       12.5 mg                     159   S-(butoxy carbonyl methyl) cysteine                                                                   I and V     Tablets as                                                                            12.5 mg                                                               in Ex. 54-56                        160   S-(methoxy carbonyl ethyl) cysteine                                                                   II          "       15.0 mg                     161   S-(methoxy carbonyl propyl) cysteine                                                                  I and V     "       15.0 mg                     162   S-(methoxy carbonyl butyl) cysteine                                                                   I and V     "       15.0 mg                     163   3-(1-naphthyl 2-methylthio) alanine                                                                   I           "       15.0 mg                     __________________________________________________________________________

Table II, below, lists active compounds which are cysteamine derivativesand which are usefully employed in the present invention. Table IIidentifies the general method by which the active compounds are preparedin accordance with Methods I-VIII disclosed hereinbefore, as well asrepresentative compositions in which they are included for oraladministration to humans having a scalp characterized by excessivesecretion of sebum to reduce said excessive secretion so as to improvethe condition of the scalp and to improve the appearance of the hair.

                                      TABLE II                                    __________________________________________________________________________                                  Method of                                                                             Form of Amount in                       No.   Active Compound         Preparation                                                                           Composition                                                                           Composition                     __________________________________________________________________________    1     2-methylthio ethylamine (cinnamate)                                                                   I or IV Drops as in                                                                           0.75 g                                                                Ex. 27-54                               2     2-methyl thio ethylurea I or VIII                                                                             "       0.75 g                          3     N-(2-methylthio ethyl) p-acetamido                                                                    VII, IV or I                                                                          "       0.75 g                                benzamide                                                               4     N-(2-methylthio ethyl)p-acetamido                                                                     VII, IV or I                                                                          "       0.75 g                                benzenesulfonamide                                                      5     N-(2-propylthioethyl)-p-methoxy                                                                       VII, IV or I                                                                          "       0.75 g                                benzamide                                                               6     N-(butylthio ethyl) nicotinamide                                                                      I or VII                                                                              "       1.0 g                           7     N-(2-dodecylthio ethyl) p-butoxybenzamide                                                             VII or IV                                                                             "       1.0 g                           8     N-(2-methylthio ethyl) p-toluenesulfonamide                                                           VII or IV                                                                             "       1.0 g                           9     N-(2-isopropylthio ethyl) propionamide                                                                VII or IV                                                                             "       1.0 g                           10    N-(2-octylthio ethyl) acetamide                                                                       VII or IV                                                                             "       1.0 g                           11    N-(2-butylthio ethyl) methanesulfonamide                                                              VII or IV                                                                             "       1.0 g                           12    N-(2-isopentylthio ethyl)butane                                                                       VII or IV                                                                             "       1.25 g                                sulfonamide                                                             13    bis 1,4-(2-acetamido ethylthio)                                                                       I or IV "       1.25 g                                2,3-butanediol                                                          14    2-hexadecylthio ethylamine hydrochloride                                                              I or IV "       1.25 g                          16    2-allylthio ethylamine malate                                                                         I       Drops as in                                                                           1.25 g                                                                Ex. 27-34                               17    9-octadecene 2-ylthio ethylamine                                                                      I       "       1.25 g                                hydrochloride                                                           18    2-dodecylthio ethylamine hydrochloride                                                                I or IV "       1.25 g                          19    2-isopentylthio ethylamine mandelate                                                                  I or IV "       1.25 g                          20    2-octadecylthio ethylamine salicylate                                                                 I or IV "       1.50 g                          21    2-β-hydroxyethyl thio ethylurea                                                                  I or VIII                                                                             "       1.50 g                          22    2-β-hydroxyethylthio ethylamine                                                                  I or IV "       1.50 g                                hydrochloride                                                           23    2-(2,3-dihydroxy propylthio)ethylamine                                                                I or IV "       1.50 g                                p-toluenesulfonate                                                      24    2-(2-hydroxy propylthio)ethylamine                                                                    IV      "       1.50 g                                oxalate                                                                 25    N-(2-methylthio ethyl)phenylacetamide                                                                 VII     "       1.50 g                          26    2-(2,2-dimethoxy ethylthio) ethylamine                                                                I       "       1.50 g                                hydrochloride                                                           27    2-(2,2-dimethoxy ethylthio) ethylamine                                                                I       "       2.0 g                                 undecylenate                                                            28    2-(2,2-diethoxy ethylthio) ethylamine                                                                 I       "       2.0 g                                 undecylenate                                                            29    2-(2,2-diethoxy ethylthio)ethylamine acetate                                                          I       "       2.0 g                           30    2-undecenylthio ethylamine                                                                            I       Drops as in                                                                           2.0 mg                                                                Ex. 27-34                               31    2-β-ureidoethylthio ethylamine hydrochloride                                                     I or IV "       2.50 mg                         32    2-β-acetamidoethylthio ethylamine tropate                                                        I or IV "       2.50 mg                         33    2,2'-thio diethylamine fumarate                                                                       I or IV "       3.0 mg                          34    2,2'-thio diethylurea   VIII or I                                                                             Ampoules as                                                                           50 mg                                                                 in Ex. 35-41                            35    3-β-aminoethylthio propylamine hydro-                                                            I or IV "       50 mg                                 chloride                                                                36    S-β-ureidoethyl thiocarbamate                                                                    VIII    "       50 mg                           37    2-ethoxycarbonylthio ethylamine                                                                       I       "       50 mg                                 hydrochloride                                                           38    2-dimethylamino carbonylthio ethylamine                                                               I       "       50 mg                                 sulfate                                                                 39    2-butoxycarbonyl methylthio ethylurea                                                                 I or IV "       50 mg                           40    2-ethyloxycarbonylmethylthio ethylamine                                                               V       "       50 mg                                 hydrochloride                                                           41    6-β-aminoethylthio hexanoate of methyl                                                           I       "       50 mg                                 hydrochloride                                                           42    5-β-aminoethylthio pentanoic acid                                                                II      "       50 mg                           43    2-phenylthio ethylamine dihydrogen phosphate                                                          I or IV "       50 mg                           44    2-p-t-butylphenylthio ethylamine                                                                      I or IV "       50 mg                                 trichloracetate                                                         45    2-p-methoxyphenylthio ethylamine                                                                      I or IV Ampoules as                                                                           50 mg                                 ditartrate                      in Ex. 35-41                            46    2-tolylthio ethylamine hydrobromide                                                                   I or IV "       50 mg                           47    2-(1-biphenyl thio) ethylamine                                                                        I or IV "       50 mg                                 hydrochloride                                                           48    2-N-pentachlorophenylthio ethyl                                                                       I or IV "       50 mg                                 acetamide                                                               49    2-benzylthio ethylamine malate                                                                        I or IV "       50 mg                           50    2-benzylthio ethylamine nicotinate                                                                    I or IV "       50 mg                           51    2-benzylthio 2-methyl propylamine                                                                     I       "       50 mg                                 hydrochloride                                                           52    2-benzylthio propylamine lactate                                                                      I       "       50 mg                           53    N-(2-benzylthio ethyl)nicotinamide                                                                    VI      "       50 mg                                 hydrochloride                                                           54    N-(2-benzylthio ethyl) 10-undecene amide                                                              VII or IV                                                                             "       50 mg                           55    N-(2-benzylthio ethyl) hexadecanamide                                                                 VII or IV                                                                             "       50 mg                           56    S-β-aminoethyl mercaptobutyric acid                                                              I       "       50 mg                           57    N-(2-benzylthio ethyl)formamide                                                                       VII     "       50 mg                           58    N-(2-benzylthio ethyl)phenylacetamide                                                                 VII or IV                                                                             "       50 mg                           59    N-[2-(2,6-dimethyl phenyl)ethyl]                                                                      VII or IV                                                                             "       50 mg                                 hexanamide                                                              60    2-o-aminophenylthio ethylamine succinate                                                              I or IV Ampoules as                                                                           50 mg                                                                 in Ex. 35-41                            61    N-(2-benzylthio ethyl) glutamine                                                                      VII     "       50 mg                           62    S-β-aminoethyl mercapto acetic acid                                                              I       "       50 mg                           63    (3-S-β-aminoethyl) mercapto propionic acid                                                       II      "       50 mg                           64    (3-S-γ-amino propyl) mercapto acetic acid                                                       I       "       50 mg                           65    S(2-p-methoxybenzamido ethyl) mercapto                                                                I       Lozenges as                                                                           7.00 mg                               acetic acid                     in Ex. 42-48                            66    2-(2-naphtyl methylthio) ethylamine                                                                   I or IV "       7.00 mg                               hydrochloride                                                           67    2-(2-naphtyl methylthio) ethylamine                                                                   I or IV "       7.00 mg                               disuccinate                                                             68    (2-thenyl) 2-thio ethylamine hydrobromide                                                             I or IV "       7.00 mg                         69    2-N-acetyl (2-thenylthio- ethylamine                                                                  VII or IV                                                                             "       7.00 mg                         70    2-o-chlorobenzylthio ethylamine hydro-                                                                I or IV "       15.0 mg                               chloride                                                                71    2-p-chlorobenzylthio ethylamine glycolate                                                             I or IV "       15.0 mg                         72    2-o-fluorobenzylthio ethylamine hydro-                                                                I or IV "       15.0 mg                               chloride                                                                73    2-furfurylthio ethylamine hydrochloride                                                               I or IV "       15.0 mg                         74    2-tetrahydrofurfurylthio ethylamine p-                                                                I or IV "       15.0 mg                               amino-benzoate                                                          75    2-β-phenylethylthio ethylamine                                                                   I or II Lozenges as                                                                           15.0 mg                               glutamate                       in Ex. 42-48                            76    2-diphenylmethylthio ethylamine                                                                       I or III                                                                              "       17.5 mg                               hydrochloride                                                           77    2-triphenyl methylthio ethylamine                                                                     I or III                                                                              "       17.5 mg                               hydrochloride hemihydrate                                               78    2-(2-pyridyl ethylthio)ethylamine                                                                     I or II "       17.5 mg                               hydrochloride                                                           79    2-(2-p-toluene sulfonamido ethylthio)                                                                 VII     "       17.5 mg                               pyridine N-oxide                                                        80    2-β-aminoethylthiomethyl pyridine N-oxide                                                        I       "       17.5 mg                               dihydrochloride                                                         81    2-β-aminoethylthio pyridine N-oxide                                                              I       "       17.5 mg                               hydrochloride                                                           82    2,4-dichloro 2-benzylthio ethylamine                                                                  I or IV "       20.0 mg                               aspartate                                                               83    N-[2-(3,4-dichloro benzylthio)ethyl]                                                                  VII or IV                                                                             "       20.0 mg                               butyramide                                                              84    N-[2-(2,6-dichloro benzylthio)ethyl]                                                                  VII or IV                                                                             "       20.0 mg                               dodecanamide                                                            85    N-[2-(3,5-dichloro benzylthio)ethyl]                                                                  VII or IV                                                                             "       20.0 mg                               trifluoroacetamide                                                      86    2-o-methoxy benzylthio ethylamine                                                                     I or IV "       20.0 mg                               hydrochloride                                                           87    2-p-ethoxybenzylthio ethylamine                                                                       I or IV Lozenges as                                                                           22.5 mg                               hydrochloride                   in Ex. 42-48                            88    N-[2-m-fluorobenzylthio ethyl]                                                                        VII     "       22.5 mg                               chloroacetamide                                                         89    2-p-bromobenzylthio ethylamine succinate                                                              I or IV "       22.5 mg                         90    2-(3,4-dimethoxy benzylthio)ethylamine                                                                I or IV "       22.5 mg                               malate                                                                  91    2-(3,4-methylenedioxy benzylthio)ethylamine                                                           I or IV "       22.5 mg                               hydrochloride                                                           92    2-(2,4-dichloro cetylthio)ethylamine                                    93    2-(3,4,5-trimethoxy benzylthio)ethylamine                                                             I or IV "       25.0 mg                               hydrocinnamate                                                          94    2-p-methoxy benzylthio ethylamine                                                                     I or IV "       25.0 mg                               salicylate                                                              95    2-o-methylbenzylthio ethylamine phenyl-                                                               I or IV "       25.0 mg                               acetate                                                                 96    N-[2-p-dimethylaminobenzylthio ethyl]                                                                 VII or IV                                                                             "       25.0 mg                               methane-sulfonamide                                                     97    2-p-phenoxybenzylthio ethylamine hydro-                                                               I or IV "       25.0 mg                               chloride                                                                98    2-β-aminoethylthio pyridine hydrochloride                                                        I or IV Chewable                                                                              1.90 g                                                                pellets as                                                                    in Ex. 49-53                            99    2-benzylthio ethylamine citrate                                                                       I or IV Chewable                                                                              1.90 g                                                                pellets as                                                                    in Ex. 49-53                            100   N-[2-benzylthio ethyl] 2,4-dihydroxy                                                                  VII     "       1.90 g                                3,3-dimethyl butyramide                                                 101   N-(2-benzylthio ethyl) 6,8-dihydroxy                                                                  VII     "       1.90 g                                7,7-dimethyl 5-oxo 4-aza octana-                                              mide                                                                    102   N-[2-(2-pyridyl thio)ethyl] propionamide                                                              VII or IV                                                                             "       1.90 g                          103   2-(2-pyridyl methylthio)ethylamine                                                                    I       "       2.5 g                                 dihydrochloride                                                         104   2-benzylthio ethylamine pantothenate                                                                  I or IV "       2.5 g                           105   S-(β-acetamidoethyl)mercaptoacetate of                                                           V or IV "       2.5 g                                 β-morpholinoethyl                                                  106   S-(β-phenylacetamidoethyl)mercaptoacetate of                                                     V or IV "       2.5 g                                 N'-methyl 2-piperazino ethyl                                            107   S-(β-ureidoethyl)mercaptoacetate of                                                              V       "       2.5 g                                 β-pyrrolidino-ethyl                                                108   S-(β-trifluoroacetamidoethyl)-βmercapto-                                                    V       "       3.75 g                                propionate of β-dimethylaminoethyl                                 109   2-p-nitrobenzylthio ethylamine crotonate                                                              I or IV "       3.75 g                          110   2-β-morpholinocarbonyl ethylthio ethylamine                                                      I or II "       3.75 g                                hydrochloride                                                           111   N,N-di(hydroxyethyl)S-(β-benzamido-                                                              I or IV Chewable                                                                              3.75 g                                ethyl)mercapto-acetamido        pellets as                                                                    in Ex. 49-53                            112   N[2-N'-methyl piperazino carbonylthio                                                                 I       "       3.75 g                                ethyl] acetamide                                                        113   2-(1-naphthyl thio)ethylamine hydrochloride                                                           I or IV "       3.75 g                          114   N-(3-β-ureidoethylthio propyl) succinamic                                                        VII     "       5.0 g                                 acid                                                                    115   3-allylthio propylamine I       "       5.0 g                           116   3-(2,2'-dimethoxy ethylthio)propylamine                                                               I       "       5.0 g                           117   3-(2,2'-dimethoxy ethylthio)propylamine                                                               VII or IV                                                                             "       5.0 g                                 sulfate                                                                 118   S-β-aminoethylmercapto acetic acid                                                               VII or IV                                                                             "       5.0 g                           119   The hydrochloride of S-β-aminoethyl                                                              VII or IV                                                                             "       5.0 g                                 mercapto acetic acid                                                    120   N-(2-benzylthioethyl)acetamide                                                                        VII or IV                                                                             "       6.25 g                          121   N-(2-benzylthioethyl)propionamide                                                                     VII or IV                                                                             "       6.25 g                          122   N-(2-benzylthioethyl)butyramide                                                                       VII or IV                                                                             "       6.25 g                          123   N-(2-benzylthioethyl)methanesulfonamide                                                               VII or IV                                                                             "       6.25 g                          124   N-(2-benzylthioethyl)ethanesulfonamide                                                                VII or IV                                                                             "       6.25 g                          125   N-(2-benzylthioethyl-propanesulfonamide                                                               VII or IV                                                                             "       7.50 g                          126   N-(2-benzylthioethyl)butanesulfonamide                                                                VII or IV                                                                             Chewable                                                                              7.50 g                                                                pellets                                                                       as in                                                                         Ex. 49-53                               127   S-(2-p-acetamidobenzenesulfonamido ethyl)                                                             I or IV "       7.50 g                                mercapto acetic acid                                                    128   S-(2-p-acetamidobenzamido ethyl) mercapto                                                             I or IV "       7.50 g                                acetic acid                                                             129   N-(2-thenylthioethyl)acetamide                                                                        VII or I                                                                              "       7.50 g                          130   2-benzylthio propylamine                                                                              I       "       7.50 g                          131   2-benzylthio 2-methyl propylamine                                                                     I       Tablets as in                                                                         6. mg                                                                 Ex. 54-56                               132   2-(2-p-toluenesulfonamido ethylthio)                                                                  VII     "       6. mg                                 pyridine N-oxide                                                        133   S-(2-p-butoxybenzamidoethyl)mercapto acetic                                                           I or IV "       6. mg                                 acid                                                                    134   2-t-butylthio ethylamine hydrochloride                                                                III     "       6. mg                           135   2-methoxycarbonyl methylthio ethylamine                                                               V       "       6. mg                                 hydrochloride                                                           136   2-ethoxycarbonylmethylthio ethylamine                                                                 V       "       10. mg                                hydrochloride                                                           137   2-propoxycarbonylmethyl thio ethylamine                                                               V       "       10. mg                                hydrochloride                                                           138   2-butoxycarbonylmethylthio ethylamine                                                                 V       "       10. mg                                hydrochloride                                                           139   2,2'-thio diethylamine dihydrochloride                                                                I or IV Tablets as                                                                            10. mg                                                                in Ex. 54-56                            140   3-(2-aminoethylthio)alanine hydrochloride                                                             I or IV "       10. mg                          141   2-benzylthio ethylammonium diacid phosphate                                                           I or IV "       12.5 mg                         142   2-methylthio ethylamine I or IV "       12.5 mg                         143   N-(methylthioethyl) p-acetamidobenzamide                                                              VII or IV                                                                             "       12.5 mg                         144   N-(2-methylthioethyl)nicotinamide                                                                     "       "       12.5 mg                         145   N-(2-methylthioethyl)benzamide                                                                        "       "       15. mg                          146   N-(2-methylthioethyl) p-methoxybenzamide                                                              "       "       15. mg                          147   N-(2-methylthioethyl) p-butoxybenzamide                                                               "       "       15. mg                          148   N-(2-methylthioethyl) butyramide                                                                      "       "       15. mg                          149   N-(2-methylthioethyl) propionamide                                                                    "       "       15. mg                          150   N-(2-methylthioethyl) acetamide                                                                       "       "       17.5 mg                         151   N-(2-methylthioethyl) butanesulfonamide                                                               "       "       17.5 mg                         152   N-(2-octylthioethyl) methanesulfonamide                                                               "       "       17.5 mg                         153   2-cetylthio ethylamine hydrochloride                                                                  I       "       17.5 mg                         154   2-(2-hydroxyethylthio) ethylamine                                                                     I or IV "       17.5 mg                               hydrochloride                                                           155   2-methylthio ethylamine phenylacetate                                                                 I or IV "       20. mg                          156   2-methylthio ethylamine undecylenate                                                                  I or IV "       20. mg                      

What is claimed is:
 1. A method for treating a scalp, characterized byan excessive secretion of sebum, to improve the condition thereof byreducing said excessive secretion of sebum comprising orallyadministering to a human being having a scalp so characterized atherapeutic composition comprising an ingestible carrier admixed with anon-toxic active compound selected from the group consistingof2-methylthio ethylamine cinnamate, 2-hexadecylthio ethylaminehydrochloride, 2-allylthio ethylamine malate, 9-octadecene-2-ylthioethylamine hydrochloride, 2-dodecylthio ethylamine hydrochloride,2-isopentylthio ethylamine mandelate, 2-octadecylthio ethylaminesalicylate, 2-β-hydroxyethylthio ethylamine hydrochloride,2-(2,3-dihydroxy propylthio) ethylamine p-toluenesulfonate, 2-(2-hydroxypropylthio) ethylamine oxalate, 2-(2,2-dimethoxy ethylthio) ethylaminehydrochloride, 2-(2,2-dimethoxy ethylthio) ethylamine undecylenate,2-(2,2-diethoxy ethylthio) ethylamine undecylenate, 2-(2,2-diethoxyethylthio) ethylamine acetate, 2-undecenylthio ethylamine,2-β-acetamidoethylthio ethylamine tropate, 2,2'-thio diethylaminefumarate, 3-β-aminoethylthio propylamine hydrochloride, 3-allylthiopropylamine, 3-(2,2'-dimethoxy ethylthio) propylamine, 3-(2,2'-dimethoxyethyl thio) propylamine sulfate, 2-t-butylthio ethylamine hydrochloride,2,2'-thio diethylamine dihydrochloride, 2-methylthio ethylamine,2-cetylthio ethylamine hydrochloride, 2-methylthio ethylaminephenylacetate and 2-methylthio ethylamine undecylenate,said activecompound being present in an amount ranging from 0.75 to 3 percent byweight of said composition and said composition being administered at arate of 1-5 mg/kg/day based on the weight of the human being.
 2. Themethod of claim 1 wherein said active compound is 2-methylthioethylamine phenylacetate.